PDA TR54质量风险管理在制药和生物技术生产操作中的应用-2012（中英文-校对版）

Thistechnicalreportprovidesdetailedguidanceforimplementationofqualityriskmanagement(QRM)principlesthroughouttheproductlifecycle.ThereportemphasiandintegratingQRMintothedocumentsprovidedetailedexamplesofcharacteristicoperationsandhowQRMprinciplesandtoolscanbeappliedforbiotAPIs,drugproduct(liPDATechnicalReportNoQRMisintegraltoaneffecmanagement)thatcanprovideaproactive(whilealsosupportingareactive)qualityandpatientsafety.QRMfacilitatescontinuperformanceandproductqualitythroughouttheproductlifecycle(1).PerICHQ9,QualityRiskapplicationofqualitymanagementpolicies,procedures,andpracticestothetasksofassessing,controlling,communicating,andreviewingrisk."(2)Itisimportanttounderstandthatriskassessmentisnotsynonymouseffective，riskmanagementshouldholisticallyencompasstheenQRMisalivingprocessandshouldbemanagedbasedonknowledthroughouttheproductlifecycle.ICHQ9specificallyprovidesguidanceontheprinciplesandtoolsofQRM(2).ImplementationofQRMoffersmanybenefitstoindustryandregulators.Whenrisk-baseddecision-making(byregulatorsandindustry')regardingthequalityofdrugsuccessfullyintegratedintoacompany’sPQSICHQ10,whichdiscussesthepotentialopportProspectivePreventiveQualityRiskManagementProspectivePreventiveQualityRiskManagementMostlyRetrospective/CorrectiveQualityRiskManagementIntegratedQualityRiskManagementNoQualityAiskManagement前瞻性的预防性的质量风险管理的/补救的质量风险管理完整的质量风险管理无质量风险管理QRMintermsofrisk-basedapproaches.Effectiunderstandingoftheproductandproceenableacompanytoprioritizeandfocusresourcesappropriately.），sectors.Overthelastfewyears,thepharmaceuticalandbiotechnologyindustrieshavebeguntoimplementtheprinciplesandtoolssafeandefficaciousdrugproductsareconsistentlydeliveredtoev生物技术工业已经使用ICHQ9的原则和工具确保每位患者能够使用到安全有效RealizationofQRMisanevolutionaryprocess.Itrequiresaparadigmshiftinmindset，质量风险管理是不断完善发展的。在人们的工作中需要转变观念和行为。图1-1Figure1-1Exampleofa•Risksmanagedfromearlyoninthelifecycle•Increasedcompliance•Higherefficiency•Knowledgemanagement•FewersurprisesInformalQualityRiskManagement非正式的质量风险管理Thetaskforcethatdevelopedthisreportwascomprisedofexperiencedprofessionalsfromriskmanagement，manufacturing,tauthorities.Thebroaddiversityinexperienceandexpertiseinthetaskforceenabledrich,balanceddiscussionsfromindustryandregucontentinthisreportdoesnotrepresenttheQRMpThetaskforcerecognizesthattherearemanyapproachesthatcanbeusimplementationoftheICHQ9guideline.ThisreportisintendedtoalignwithICHandpresentsinformationthQRM..Theobjectiveisnottorepresentorreplaceregulatoryrequireguidance;nordoesitestablishlegallyenforceablerequir工作组认识到有许多种途径能够用来贯彻执行ICHQ9的指导方针。报告的目的ThistechnicalreportwasdistributedforpublicreviewandcommepublicationtoensureitssuitabilityasavaluableguidTheglossaryoftermsisbasedondefinitionsprovidedincurrentICH,FDandotherregulatoryguidelines,standards,orindustrypublications.Insomeavailableinsuchsources,thebestavailabledefinitiobythetaskforce.RefertoICHQ9forasummaryofthecommonriskmanagementtools.Thefollowingtermsanddefinitionshavebeenusedinthistechnical用，工作组会采纳或发展最合适的定义。适用于ICHQ9的普通风险管理工具的AsLowAsReasonablyPracticable(ALTheabilitytoreducerisk.ALARPhaspracticabilityreferstotheabilitytoreduceriskregardlessofcost.Economicpracticabilityreferstotheabilitytoreduceriskwithoutmakingtheproducttoocostlyturnoveroffacilities,systems,andequipmenttotheenduserthaexpectations.(ISPEActiveP设计要求和系统责任人的预期（ISPE原料药指南第二Recurringactivitytoincreasetheabilitytofulfillrequi提高满足需求的能力的反复性活动(ICHQ10,ISO9Aplannedsetofcontrols,derivedfromcurrthatensuresprocessperformanceandproductquality.Thecomponents,facilityandequipmentoperatingconditions,in-processcontrolproductspecifications,andthcontrol.(ICHQ10)源自现行产品和工艺理解的一组规划过的控成品质量标准，和监控与控制的关联方法与频次的相关参数与属性(ICHQ10)。Actiontoeliminatethecauseofadetectednon-conformityorotherundesirableNOTE:Correctiveactionistaketakentopreventoccurrence.(ISO9000:20注意：纠正措施是用来预防重复发生而不是预防措施用来预防发生(ISOAclassificationofanitem(e.g.,procsignificancegiventotheimpactmonitoredtoensureproductCriticalProcessParameAprocessparameterwhosevariabilityhasanimpactonacriticalquathereforeshouldbemonitoredorcontrolledtoensuretheprocessproducesthedesiredCriticalQualityAttrAphysical,chemical,biological,ormicrobioCurrentGoodManufacturingPractiPracticesandsystemsthatarerequiredtobefollowedforpharmaceutimanufacturingtoensurethattheprodriskmanagementdecisions.(ICHTheabilitytodiscoverordeterminetheexisAtoolorprocesswhichprovidesthemeanstoachieveanobjectrepresentationofconsequencesresultingfromaninitiatingevent.FailureModeandEffectsApotentialfailuremodes,theireffectsonsystem,productandprocessperfthepossiblecausesoffai1ureinordertopreventdefectsfromoccurring.Adeductivetechniqueusedtoanalyzethecausvisuallymodelshowlogicalrelationshipsbetweenfailures,humanerrors,andexternalDamagetohealth,includingthedamagethatcanoccurfromlossofproductqualityorThepotentialsourceofharm.(ISO/IECGuide51,ICHQ9)伤害的潜在来源(ISO/IEC指南5HazardAnalysisandCriticalControlPoints(Asystematic,proactive,andpreventivetoolforassuringproductquality,reliabilHazardandOperabilityAnalysisAstructured,systemarepresentriskstopersonnelorequipment,orpreventefficientopeIntendedUse/Intendeinstructionsandinformationprovidedbythemanufacturelatedtoproducts,manufacturingprocessesandcomponents.(ICHAllphasesinthelifeofaproduuntiltheproduct'sdiscontinuation(ICHQ8).Probabi1itythataneventpotentiallyleadingtoharmwilloccPreliminaryHazardAnalysiAtoolofanalysisbasedonapplyingpriorexperienceorknowlharm,aswellastoestimatetheirActiontoeliminatethecauseofapotentialnon-confopotentialsituation.NOTE:Preventiveactitakentopreventrecurrence.(ISO9000:2Confirmingthatthemanufacturingprocessasdesig确认所设计的商业生产工艺在商业化生产阶段是能够再现的(FDA工艺验证指Collectionandevaluationofdata,production,whichestablishesconsistentlydeliveringqualityproducts.Allphasesinthelifeofaproduuntiltheproduct'sdiscontinuation.(ICHQ8[R2])installed,workcorrectlyandactuallyleadtotheexpectedresults.Quofvalidation,buttheindividua1qualificationstepsalonedonoThedegreetowhichasetofinherentfulfillsrequirementstermincludessuchattQualityRiskManagemAsystematicprocessfortheassessment,cotothequalityofthedrug(medicinal)productacrosstheproductlifecycle.(ICHQ9)Atargetproductprofileisaprospectiveanddynamicsummaryofthequalitycharacteristicsofadrugproductthatideallywillbeachievedtargetproductprofileformsthebasisofdesignforthedevelopmentoftheproduct.Riskremainingafterriskc在采取风险控制措施后残留的风险（来自ISOThecombinationoftheprobabilityofoccurrenceofharmandtheseverityofthatharm.(ISO/ECGuide51)伤害发生的概率和严重性的组合（ISO/Theestimationoftheriskassociatedwiththeidentifiedhazards.(ICHQ9)Asystematicprocessoforganizinginformationtosupportariskdecisiontobemwithinariskmanagementprocess.ItconsistsoftheidentificationofhazardsandtanalysisandevaluationofrisksassociatedwithexpThesharingofinformationaboutrActionsimplementingriskmanagementdecisions.(ISOGuide73)Adeterminationofacceptanceorrejectionofrisk.qualitativescaletodeterminethesignificanceoftherisk.(ICHQ9)Thesystematicuseofinformationtoidentifypotentireferringtotheriskquestionorproblemdescription.(ICHQ9)Thesystematicapplicationofqualitymanagementpolicies,procedures,andpracticestothetasksofassessing,controlling,communicatingandreviewingrisk.(ICHQ9)ReportthatsummarizestheoutcomesoftheQRMprocess.ActionstakentolessentheprobabilityofoccurrenceofharmandtheseverityofthatReviewormonitoringofoutput/resultsoftheriskmanagementprocessconsidering(ifappropriate)newknowledgeandexperienceabouttherisk.(ICHQ9)Ameasureofthepossibleconsequencesofahazard.(ICHQ9)itselftobeaffectedbyarisk.Decisionmakersmightpurposesofthisguideline,theprimarystakeholdersarethepatient,healthcareprofessional,regulatoryauAstatisticaltermreferringtothedirectionorrateofchangeofavariable(s).(ICHQ9)3.0GeneralPrinciplesOnQualityRiskManagementApplication质量风AcombinedapplicationofICHQ8[enhancedknowledgeofproductperformanceoverarangeofmaterialattributes,manufacturingprocessoptions,andprocessparameterstofurthersuppandrisk-basedmanagementoftheproductlifecycle.），OneofthecharacteristicsofamaturePQSistheeffectiveintegrationrelevantprocessesthroughouttheproductandprocesslifecycles.Ateachphaseinthelifecycle,QRMshouldbeappliedatalevelthatiscommensuratewavailableduringthatphase,andcomplexiproductdesignandprogresstoprocessdesignastheproductadvancestoclinicommercialproduction.Riskassessmentsshouldberevilifecycle(Figure3.1-available.Additionally,QRMcanbeusefulinidentifyingaforotherproductstofacilitatecontinualimprovement.到整个生命周期（图表3.1-1）中。除此之外，质量Figure3.1-1ProductLifecycle3.1.1QualityRiskManagementApplicationDuringPharmaceuticalDevelopment药productanditsmanufacturingprocesstoconsistentlyperformanceandmeettheneedsofpatients,healthcareprofessionals,regulatoryauthorities,andinternalknowledgeandunderstandingoftheproduct.applicationofQRMcanfsystematicunderstandingofproductsandprocessesbTheappropriateuseofQRMprinciplescanservethefollowingobjectives:•Designtheproductandprocesstoreducerisktoproductqualityandt•Prioritizethepharmaceuticalproductknowledge.Attributes(CQA)(perICHQ8[R2]).ExamplesofhowtoapplyQRMprinciplesduringthedevelopmentphaseinclude:•Developingaprocessthatroutinelymeetscriticalqualityattr•Identifyingcriticalprocessparameters(CPP)andmateri•SupportingtheselectionandsubsequentqualificationofsupplierRiskmanagementtoolssuchasRiskRankingandFilterinanalyzedusingaqualitative/semi-quantitativeriskmanagPreliminaryHazardAnalysis(PHA).FailureModeandEffectsAnalysis(alsobeuseful,particular1yduringthelaterstagesofdevelopment.PerICHQI0,thegoaldevelopmentandmanufacturingorbefollowingobjectives:•AssessandmanageriskstoprocessandproductqualityasaresmanufacturingscaleTheoutcomesoftheQRMprocesscanbeusedtopreventiveactionstoappropriatelymanageidentifmanagementofprocesscontrolsduringthetechnologytransferprocess.QRMcanbeusedtodevelopariskbasedvalidationmasterplantodqualificationandvalidationactivities.DuririskmanagementtoolssuchasanFMEAorHazardandO(HAZOP)are0ftenused.3.1.3QualityRiskManagementApplicationDurinrealizationwithsuitableprocessperformance，establishandmaintainastateofcontrol,faciliitatecontinualimprovementan•Establishrobustconimprovement，toensureconsistentprocessperformaDuringcommercialmanufacturing,QRMcanbeausefulprocessdecision-makingas-sociatedwithchangecontrintheselectionandmanagementofsuppliersandvendors,andmanagingrisksrelatedtointernalandcontractmanufacturingoperations,toproductavailabilitythroughouttheproductldistribution,transportation,chainofgeopoliticalissues,complianceSection5.4,QRMApplicationinMaterialsManagemen3.1.4QualityRiskManagementApplicatPerICHQlO,thegoalofProductDiscontinuationactivitiesisto"managetheterminalstageoftheproductlifecycleeffecdiscontinuationactivitiescanservethefollowingobjec•Ensureriskstopatientsaremainsonthemark•Identifyandmanagerisksrelatedtotransitioningpatientstoalternat3.2ProactiveandReactiveApplicationofQualityRiskManagement质量风险管andmanagementofrisks.Retrospectiveorreactiveapplicatiolngeneral,theearlierrisksareidentified,themoreeffectivetheirmanagForexample,ifariskisidentifiedduringthedevelopmentofdesignspecificationsforasystem,thesystemcanbedesignedtoreduceoreveneliminatetheristhesameriskisnotidentifieredesignofthesystemcanbechallengingandlikelybemorecostlythanifthesystemhadinitiallybeendesignedtomanagetheriskappropriately.Thiswouladditiontothecostofmanagingpotentialharmtoproductquaduetothatriskduringcommercialoperation.prospectivelyandriskassessmentsmayneedtoberetrospectively.Exampleswouldbenmanufacturingprocess.lntheseinstances,deductiveriskmanagementtoolslikeFaultdeterminethecontributiqualitywillconsequentlyneedtobemanagedretrospe然而,某些情况下,并非所有的风险都可以如预期般识别，这样就需要执行回顾性的潜在风险。在这些实例中,演绎的风险管理工具如失效和事件树分析(FTA/ETA),FMEA,或鱼骨图分析可以用来确定事件的相关因素,接下来任何影响产品existingoperationsandappropriatdeviatefromregulations,justifybadpractices,defendpracticesthatneedtobecorrected,orasasuManufacturingPractices(cGMPs)isam质量风险管理不是独立于质量系统的元素，而应该整合到现存的规程中，作为3.3FormalityoftheQualityRiskManagementProcess质量风险管理程序的正式流程OneoftheprinciplesofQRMasperlCHQ9isthatthelevelofeffort,formalityanddocumentationoftheQRMprocessshouldbecommensuratewiththelevelofrisk.ltisneitheralwaysapproprprocess(2).Theuseofinformalriskmanagementprocesses(usingempiricaltoolsorfframeworkforpreviouslyundocinformalriskmanagementprisk-basedapproachcanrangefromadocumeassessmentmethodology(SeeFigure3.3-1).Figure3.3-1RigorandFormalityofQRMApproaches如：过程危险分析逐渐严谨&正式化decisiontree)Thedegreeofriskmanagementrigorandformalityrequiredisinfluencedbyacombinationofmanyfactors,including(butnotlimitedto):•Criticality(e.g.,impactonpatientsafetyorproductquality)ofthe•Complexityoftheissue,proce•Availabilityofrelevanthistoricaldataandrelated•LevelofavailableprocessknowledgeandexperienceTheriskassessmentformalityspectrumcanrangeintherigorandformalityoffacilitation,subjectmatterexperts(SMshowninFigure3.3-Figure3.3-2RigorandFoMaybeexistingteam,group,组成专门的相关项目专家组Recongnizedmethodoptio随意选取或定制被承认的方法单独的报告，或者跟其他受package)可能整合到现存的受控GMP文件中（不包括：变更控制3.4EstablishingaQualityRiskManagementPolicyQRMpolicyestablishesthecompany'sQRMphilosophyandguidestheincorpofQRMrequirementsandprinciplesintotheQualitySystemrelatedto:ICHQ10阐述了质量风险管理作为一种有用的工具合并到质量系统中的重•Applicabilityofriskmanagement•Accountabilityandresponsibilityformanaginganddeterminingris•Riskreviewsand3.5ManagementCommitmentessential.TopmanagementendorsestheincorporationofQRMintotheorganizaimplementationofQRMprinciplesandactivities,andprovreceivedtheapplicabletraining.useofQRMisencouraged,itsbenefitsunderstood,itstoolsappliedappropriately,andvariousfunctionsanddepartmentsoftheirorganization.TheultimategoalistoincorporateQRMintoeverydaypractices,integratedintothesafety,heaTofacilitateachievingthisgoaltheo•Havetheresponsibilitytocreateandmaintain•Canperformri•Canreviewandapprovetheassessreductionandriskacceptancedecision•Areresponsibleforcommunicatingtheoutputoftheriskassessments.3.6UnderstandingtheOrganizationandHowitContextualizesRiskTodevelopasharedunderstandingoftheapplicationofQRMstakeholders,organizationsneedtodeandregulatoryexpectationsAnevaluationofthecurrentunderstandingofQRMintheorganwrittenpoliciesandprocedures,practexistingorrelatedQRMactivitiesshouldbereviewedforevidenceofQRMintothecompany'sQualitySydeviationmanagement，productdevelopment将当前组织对质量风险管理的理解进行评估3.7IntegrationintoOrganizationalProcIntegrationofQRMintoanorganizprocess.PracticalrecommendationsrelatedtoimplementationofQRMmaythefollowing:•Performingagapanalysisoncurrentguidelines,identifywheresystemsarecurrentlyemployingQRMmeasurementofthelevelofrisk•对当前指导原则、程序和操作规程执行差距分析，可以识别什么系统当前需要•CreatingQRMpoliciesandproceduresbaseduponthegapanalyincludingQRMmethodsandsupportingstatisti•Pilotingthepoliciesandacceptabilityprocess,andreportingmechanismsfittheneedsoftheorganization.•Deployingthepoliciesmulti-leveltrainingstrateg•High-levelawareness/QRMoverviewtrainingforgeneralemployincludehands-ontrainingwithreallifeappl•集中对方针，规程和风险管理的基本工具进行培训。其中包括对真实的案例进•Creationofinternalauditprodecisionscomplywiththeestablishedstandardsand•建立识别质量风险管理活动的内部审计规程，得到符合已建立标准和规程的决Attitude没有正式的规程FearOfBlame没有意识到不AdHocUseof临时使用独立Belief被动的，处理&理解并应用阶段标记盒子的方法依赖法规符合性纳入和整合阶段风险管理纳入RobustRisk稳定的风险管常规审核并改善创新的，自信和合适的风险3.8EstablishingCommunicationandReportingMechanismsTofullyintegrateQRMintothcommunicationandrepimplementationofQRMwhentheyareabletoqumanywaystoaccomplishthis,includingtheuseomemoranda.Companiesshouldconsidertheadditionofriskmanagementasanagendatopicfortheirperiodicmanagementmeetingsatallleve的信息流进行识别和沟通新风险的发展变化。有很多方法可以做到这一点,包括Feedbackloopsaretwo-wayinthatasnewrisksareidentifiedtheyarecinternallyandthatproductbaseduponthatinformation.externalcommunicationswiththepublicandregulataoryagencies,ifrequired.反馈循环都是双向的,随着新的风险得到识别会引起内部沟通,而产品和工艺会根Thereshouldbeamethodtocaptureproductandprocessriskthrochoosestocapturetheoverallresidualriskshouldbculture,documentationpracticesandthepotentialimpactofproductand3.9RolesandResponsibilitieFormalQRMactivitiesareusuallyundertakenbymulti-disciplinaryteamsandshouldincludeSMEsrepresentingrelevantfunctions(e.g.qualityunit,businessdevelopment,engineering,regulatoryaffairs,productionoperations,salesandmarketinstatistics,clinicalsafety).Asinglepersonm•Facilitatorswhoareknowledgeableabout,andwillfacilitatetheQ•Asmuchaspossible,facilitatorsshouldbeindependentfromtheprocessbeingriskassessedinordertomaintainobjectivityinfacilitation(expertsshouldnotfacilitateifpossibleinordertomaintainobjectiviKnowledgeofcognitiveandotherfactors,suchashumanheuristics,mayaffectdecision-makingduringQRMactivities(suchasbrainstormingandprobabilityofoccurrenceestimation);thisunderstandingandabilitytomanageitappropriatelycanbeparticularlyusefulforfacilitators.•当进行工艺风险评估时，促进者应尽可能保持独立，以在促进过程中保持客观•QRMLeadwhomaybeindependentfromthefa•Leadingthedevelopmentandcompmanagementplansandrepo•EnsuringthattheoutcomesoftheQRMprocessareapprovedappropriatedecisionmakersandimp•SubjectmatterexpsupportQRMactivities，includingriskassessment,determicontrolmeasuresandtheirimplemendecisions(2).Decisionmakersshouldbeaccountab•EnsuringthataQRMprocessisdefined,includingtheimplementationofidentifiedriskcontrolmeasures.•Reviewingandapprovingtheomakingriskcontrol(riskreductionandriskacceptance)decision•回顾和批准风险管理活动的结果，包括制定风险控制（降低风险和接受风险）见Heuristicsarecognitivebehaviorsthatcomeintoplaywinthepresenceofuncsignificantbiasanderrorsinjudgment.Humanheuristicsgreatlyinfluenceaperceptionofrisk(4)andinevitablytheiropinionofthemagnitudeofthecontributingprobabilitiesandseverities.Agreatdealofresearchhasbeenperexperimentalpsychologistsintohowrisksarepercfactors(5)seemtocontroutputofriskanalysisexercises:偏见和错误的来源。人类启发极大地影响一个人的风险感知（4）和不可避免地知做了大量的研究。在这方面，有三个主要因素（5）似乎有助于这种启发式的1.Degreeof"dreadfulnes2.Degreetowhichtheriskwasunders3.Numberofpeopleexposedtotheriskinquestion.perceived.Therearevarioustypesofheuristics,butthreeofthemare:Theheuristicofavailabilityrelatestothefactthatpeopletendtojudgethelikelihoodofaneventintermsofhoweasilytheycanrecall(orimagine)examplesofthatevent.Aperson'sjudgmentconcerninganevent(intermsofitsprobabilityofoccurrenceanditsseverity)maytherefsimilarscenarios(6,7).Thismayleadtoasystematicbiasandothererrorsinjudgment.Researchhasshownthatpeopletendtounderestimatethefrequencyofverycommonhazardsandoverestimatethefrequencyofveryrarehazards(68).Theheuristicofrepresentativenessisrelatedtoaperson'sprobabilityjudgmentbeingthelarge."Inthisinstanceonecanpaymoreaignoringorpayinginsufficientattentionthatisrelevanttotheproblem(8).启发式的典型代表与被影响的人的概率判断有关，如他们“预计某种小概率行为Theheuristicofanchoringandadjustmentcomesintoplaywhenpeople'sjudgmcanbeheavilyinfluencedbythefirstapproximationofthevalueorquantitythatthey"anchor"(6,7).随后的价值偏向于“锚”Biasandvariabilityinriskperceptionareinherentlyhumantraitsandcanbebrcategorizedintothreerecognizableanthropomorphicbehaviors.Eachoftheseperceptionsshouldberecognized,andappropriatebias-mitigationstrategiesandprocessesestablishedwithintheQRMsystem.thatcouldbeconsideredvolu(i.e.withoutourowndewhicharecalculatedtobesignificantlylowerthaninvoluntaryrisks(10).Thephenomenonofhumanheuristics(unconsciousrulesofthumb)hasprofoundcapacitytobiasriskmanagementprocesses.Othatpeopletendtoassignlikelihoodintermsofhoweasilytheycanrecall(orimagine)thatorexamplesofthatevent.ofverycommonhazardsmayinfluencehowtheoutputsofQRMexmaybejudgedandacceptedbydecisionmakers,stAnexpert'sperceptionofriskcandiffermarkedlyfrpersonnellessfamiliarwiththeGenerally,laypeopletendtorthem,unfamiliar,orbeyondtheircontrol.SuchfindingsareprobablyimportanttoandstakeholderstowhomrtechnicalnatureofGMPactivitiesingeneral.Thehumancognitiveandbehavioralorigins,whichmaybiasjudgmentinthisrespect,togetherwithdetailedmeansofaddressingQRM,havebeenpreviouslydescribed(11,12).Effectivecommunicationparticularlyimportantbecausestakeholdersformjudgmentsaboutrisksbasedontheirownperceptions,andthoseperceptionsmaydifferincorporatestrategiestoaddressriskperceptionbiases.non-conformancesandtrendscontributegreatlyinreducingsubjethatheuristicsmayexertonQRMactivities.Toaddressofseveralsimple,practicalstrategieQRMexercisesandthatshouldbefeaturedinQBias•培训和教育可使决策者意识到这种偏见，包括案例学习和•如部分决策者不熟悉风险场景（例如临床药学，销售学，个别人类的启发•培训和教育可使决策者意识到主要启发的出现，包括案例学习和演示启发如何被掌握的例子。•如部分决策者不熟悉风险场景（例如临床药学，销售学，个别•只要数据被认为是可靠的，支持定量风险管理工具提供尽可能多•为旨在最大限度地减少启发的不利影响采用预先定义的规则的头脑风暴（例如，当风脑风暴作为风险评估的一部分练习时，团队的成员不应用语言表达他或她的估计得分概率，直到每个参与者有时间思考和记录自己的估计）专家层级的偏见•培训和教育可让决策者意识到这种偏见：包括学习案例和偏见演示例子。•如部分决策者不熟悉风险场景（例如临床药学，销售学，个别4.0ImplementationOfTheQualityRiskManagementProcess质量风险管理的实施PerICHQ9,themainstepsinth•Initiatingaqualityriskmanagementproce•Output/resultoftheQRMprocess(Section4.4)4.1InitiatingaQualityRiskManagementProcess启动质量风险QRMshouldincludesystematicprocessesdesignedtimprovesciencebaseddecisionmakingwithrespecttorisk.AllQRMactiwhethertheyareprospectiveorretrospectiveinnature,shouldbeadequatelyplanpriortoinitiatinganyriskassessments.Therigorinplanningshouldbecowiththeimpactofthepotentialrisksonproductqu